By means of Southern blot analysis, we have discovered that recurrence in B cell lymphoma, in particular follicular lymphoma, is derived from occult disease which is resistant to therapy. Multiple samples from patients obtained as much as ten years apart demonstrate that primary neoplasm and recurrences were derived from a common stem cell in all patients. No biclonal neoplasms were seen. Clonal evolution was frequent (42% of cases) and was characterized by secondary genetic events affecting rearranged immunoglobulin genes. Despite this, the rearranged bcl-2 locus in follicular lymphoma, a consequence of t(14;18) translocation, remained stable. To further analyze minimal residual disease, we have developed a method for detecting rare follicular lymphoma cells which elude detection by conventional Southern blot analysis. This method may prove useful for prediction of recurrence following clinical remission in follicular lymphoma. We have developed cell lines from the T cell leukemia of a patient with atexia telangiectasia. A chromosomal translocation t(14;18) is being analyzed by pulsefield electrophoresis to identify involvement of the T-alpha gene at band 14q11. Our leukemia cell lines from ataxia telangiectasia provide a model of clonal evolution of T cell neoplasms as a consequence of breakage of chromosomal fragment sites.